The role of conserved arginine and proline residues in enterovirus VP1 protein

Background: High diversity of VP1 protein among enteroviruses has been a barrier in developing universally effective antiviral drugs. To maintain structure stability during evo-lution, several residues of VP1 protein of enteroviruses are conserved. Therefore, investigation of highly conserved residues in VP1 protein may provide information for antiviral drug candi-dates against enteroviruses.Methods: To identify highly conserved amino acid sequences of the VP1 in enterovirus genus, the Consurf and CABS-flex 2.0 web software were applied. Through the combination with sec-ondary structure information, we focused on conserved amino acids of VP1 property analysis. Results: Most conserved residues of VP1 were in the interior and interacted with VP2, VP3 and VP4 capsid proteins. Structure of EV-A71 (PDB code 4AED) showed conserved residues were at hydrophobic pocket and close to the junction between the loop and 0-barrel. Interestingly, arginine was the most common conserved residue of VP1. Proline was the second most common conserved residue and was found in the loop and 0-barrel intersection areas. VP1 protein flex-ibility was associated with the secondary structure. Conserved residues of VP1 in 0-barrel showed significantly low flexibility.Conclusion: Through large scale sequence analysis, we identified the amino acid distribution and location of conserved residues in VP1. This knowledge can be extrapolated for the Entero-virus genus and may contribute to developing the potential compound as an anti-enteroviral agent.Copyright (c) 2022, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

By conducting large-scale sequence analysis, researchers identified the distribution and location of conserved residues in VP1 protein of enteroviruses, which is important for the development of antiviral drug candidates against enteroviruses.